New two-photon activated photodynamic therapy sensitizers induce xenograft tumor regressions after near-IR laser treatment through the body of the host mouse.
OBJECTIVE
The aim of this study was to show that novel photodynamic therapy (PDT) sensitizers can be activated by two-photon absorption in the near-IR region of the spectrum and to show, for the first time, that such activation can lead to tumor regressions at significant tissue depth. These experiments also evaluated effects of high-energy femtosecond pulsed laser irradiation on normal tissues and characterized the response of xenograft tumors to our PDT protocols.


METHODS
Human small cell lung cancer (NCI-H69), non-small cell lung cancer (A549), and breast cancer (MDA-MB-231) xenografts were induced in SCID mice. Irradiation of sensitized tumors was undertaken through the bodies of tumor-bearing mice to give a treatment depth of 2 cm. Posttreatment tumor regressions and histopathology were carried out to determine the nature of the response to these new PDT agents. Microarray expression profiles were conducted to assess the similarity of responses to single and two-photon activated PDT.


RESULTS
Regressions of all tumor types tested were seen. Histopathology was consistent with known PDT effects, and no, or minimal, changes were noted in irradiated normal tissues. Cluster analysis of microarray expression profiling showed reproducible changes in transcripts associated with apoptosis, stress, oxygen transport, and gene regulation.


CONCLUSIONS
These new PDT sensitizers can be used at a depth of 2 cm to produce excellent xenograft regressions. The tumor response was consistent with known responses to single-photon activated PDT. Experiments in larger animals are warranted to determine the maximal achievable depth of treatment.
Starkey
Jean R
JR
Department of Microbiology, Montana State University, Bozeman, MT 59717, USA. umbjs@montana.edu
Rebane
Aleksander K
AK
Drobizhev
Mikhail A
MA
Meng
Fanqing
F
Gong
Aijun
A
Elliott
Aleisha
A
McInnerney
Kate
K
Spangler
Charles W
CW
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006415:Hematoporphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D007259:Infrared Rays; D007834:Lasers; D008297:Male; D051379:Mice; D016513:Mice, SCID; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000528:radiation effects; D010100:Oxygen / Q000378:metabolism; D010778:Photochemotherapy; D017785:Photons; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014916:Whole-Body Irradiation; D023041:Xenograft Model Antitumor Assays
D006415:Hematoporphyrins; C533568:MPA79; D017319:Photosensitizing Agents; D010100:Oxygen